1. Field of the Invention
The present invention relates to a non-aerosol, non-spray delivery apparatus and method of use thereof for delivery of a minoxidil composition or a salt thereof for the treatment and prevention of androgenic alopecia, male and female pattern baldness.
2. Description of Related Art
Minoxidil (chemical formula 2,4-diamino-6-piperidinylpyrimidine-3-oxide) is the active ingredient of Rogaine® (New Brunswick, N.J.), which is approved by the U.S. Food and Drug Administration as a safe and effective drug. It is marketed by Pfizer for the treatment and prevention of androgenic alopecia.
Numerous investigators have demonstrated that minoxidil can stimulate visible hair growth in a majority of balding subjects. The structure and use of this compound is described in U.S. Pat. No. 4,139,619 and U.S. Pat. No. 4,596,812. Minoxidil has varying degrees of efficacy for moderating androgenic alopecia, depending on the degree of baldness, its duration, the age of the patient, and on the concentration of the drug in an appropriate delivery vehicle.
There are many challenges in the topical application of pharmaceutically active agents. One major objective is to achieve percutaneous penetration of the active agent to the site of treatment. It is also desirable for the composition to have desirable cosmetic characteristics, for easy and smooth application, and for administration without a noticeable residue on the surface of the skin. It is further desirable that the composition not cause irritation or discomfort. It is still further desirable that application is convenient in terms of time requirements and in terms of necessary clean-up after application.
Topical solutions have not been satisfactory for use in treating the scalp as they tend not to remain in place long enough for satisfactory amounts of the drug to be absorbed. The solution readily runs off the site of application and therefore, it is difficult to apply controlled amounts using the minoxidil in solution form.
Formulations of minoxidil, such as jellies and ointments, have been proposed. These compositions are not pharmaceutically elegant and also are not suitable for use as treatments for stimulating the growth of hair from a cosmetic point of view. Lotion and gel topical dosage forms have the disadvantage of extended rub-in and leave oily residues.
Commercially available Rogaine®, disclosed in U.S. Pat. No. 6,946,120 includes an aerosol foam, which is filled into a pressurized container together with a propellant fluid. The composition is foamed prior to the application by means of a propellant fluid.
Aerosol containers are in widespread use as liquid dispensing devices. However, aerosol containers require the use of a pressure container and a propellant fluid to create foam. Propellants provide the appropriate vapor pressure within aerosol containers for the expulsion of the formulation as a spray or semisolid when the valve is opened. Typical propellants include liquefied petroleum gases; such as mixture of propane, isobutene, and n-butane; chlorofluorocarbons; methyl ethyl ether; and dimethyl ether, which are flammable, harmful and toxic volatile organic compounds. Further, it is known that the propellant fluid frequently constitutes a source of environmental pollution and sometimes the aerosol container represents a hazard when disposed of since the propellant material are explosive or flammable. Generally, chlorofluorocarbons are banned from use due to their ozone depletion effect, liquefied petroleum gases are flammable, and other propellants such as nitrous oxide may have physiological effects.
Still further, aerosol containers can not be completely emptied or refilled, increasing waste. Aerosol containers are discarded once the supply of liquid dispersant is exhausted or when the supply of propellant material has been used to the extent that there is no longer sufficient pressure within the container to discharge the liquid as intended. Further, pressure containers can only be cylindrical, drastically limiting the choice of container shape. An additional disadvantage is that pressure containers are more expensive than non-pressurized containers and have higher manufacturing costs.
Patents related to the current invention are summarized here.
Aerosol Foam
T. Wai-Chiu So, et. al., “Pharmaceutical Composition”, U.S. Pat. No. 6,946,120 B2 (Sep. 20, 2005) describe a pharmaceutical composition for topical administration including at least five percent by weight of a piperidinopyrimidine derivative or an acceptable salt thereof, an acid, a solvent composition including water, a lower alcohol and co-solvents consisting of aromatic and polyhydric alcohols, where the co-solvent includes less than approximately ten percent by weight of propylene glycol.
Foam Spray
E. Jacques, et. al., “Minoxidil Pharmaceutical Foam Formulation”, U.S. patent application no. 2005/0079139 A1 (Apr. 14, 2005) describe a pharmaceutical foam formulation in a dosage form including at least one active ingredient selected from the group consisting of minoxidil, minoxidil sulfate, other soluble minoxidil salts, a surfactant, and water; the formulation being adapted to form a foam when administered by spraying.
Aerosol Liquid Spray
P. Cronk, et. al., “Continuous Spray Scalp Therapy and Dispensing Systems for Same”, U.S. patent application no. 2008/0206156 A1 (Aug. 28, 2008) describes continuous spray medications, spray medication dispensing systems, and methods for treating alopecia, in which a continuous mist of a scalp medication, such as minoxidil, finesteride, copper peptides, DHT inhibitors and/or androgen receptor blockers, disposed within a pharmacologically acceptable carrier solution, is administered in an amount sufficient to stimulate or maintain hair growth.
P. Uster, et. al., “Non-crystalline Minoxidil Composition”, U.S. Pat. No. 5,030,442 (Jul. 9, 1991) describe an aqueous, non-crystalline minoxidil composition for topical use containing minoxidil complexed with an amphipathic compound, oleic acid, and acceptable excipients, which has improved flux through human cadaver skin and is formulated in an aqueous vehicle or dispersed in fluorochlorocarbon solvent for spray delivery.
P. Uster, et. al., “Non-crystalline Minoxidil Composition, its Production and Application”, U.S. Pat. No. 4,828,837 (May 9, 1989) describe an aqueous, non-crystalline minoxidil composition for topical use containing minoxidil complexed with an amphipathic compound containing a single lipophilic chain moiety and a sulfate, sulfonate, phosphate and phosphonate polar moiety, and having a pK less than five. the composition is formulated in ointment form, in an aqueous vehicle, or dispersed in a fluorochlorocarbon solvent for spray delivery.
Aqueous Vehicle
J. Cappello, “Topical and Transdermal Treatments Using Urea Formulation”, U.S. Pat. No. 7,803,357 B2 (Sep. 28, 2010) describes a topical application of a composition of urea and a chemotherapeutic agent such as sclerosing agents, vasodilators, botulinum toxin, and minoxidil that is effective in treating spider veins, erectile dysfunction, facial wrinkles, hair loss, and baldness.
S. Malek, “Topical Administration Carrier Composition and Therapeutic Formulations Comprising Same”, U.S. Pat. No. 7,749,489 B2 (Jul. 6, 2010) describes a topically administered carrier composition including water, glycerin, and polysorbate, which retards the evaporative losses of the solvent component and systemic migration losses of the active ingredient to provide sustained topical action for use in formulations containing active ingredients, such as minoxidil.
K. Hallam, et. al., “Methods and Compositions for the Promotion of Hair Growth”, U.S. Pat. No. 6,465,514 B1 (Oct. 15, 2002) describe compositions, medicaments, and methods for the promotion of hair growth, topically applied to the scalp by use of an eyedropper or other suitable means, including either local anesthetics of the secondary and tertiary amino type and/or niacin. The compositions and medicaments include minoxidil and either procaine hydrochloride or niacin or procaine hydrochloride and niacin in a non-sulfur-containing carrier.
C. Chidsey, III, et. al., “Methods and Solutions for Treating Male Pattern Alopecia”, U.S. Pat. No. 4,596,812 (Jun. 24, 1986) describe a method for treating male pattern baldness, which includes regular topical application to the human scalp of a composition containing 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine as one of its active ingredients.
Gel/Ointment/Cream
L. Pena, et. al., “Compositions of Minoxidil”, U.S. Pat. No. 7,442,369 B1 (Oct. 28, 2008) describe novel compositions comprising minoxidil, a thickening agent, and a pharmaceutically acceptable solvent; a process for making a gel composition including minoxidil; and methods for using the compositions for treating and preventing hair loss in a patient.
C. Samour, “Method for Treating Hair Loss”, U.S. Pat. No. 5,620,980 (Apr. 15, 1997) describes the combination of minoxidil and 2-n-nonyl-1,3-dioxolane for promoting hair growth when applied once daily.
L. Pena, “Minoxidil Gel”, U.S. Pat. No. 5,225,189 (Jul. 6, 1993) describes a pharmaceutical gel containing minoxidil for topical application.
J. Grollier, “Composition in the Form of a Gel for Inducing and Stimulating Hair Growth and for Decreasing Their Loss, Based on Piperidinopyrimidine Derivatives”, U.S. Pat. No. 4,820,512 (Apr. 11, 1989) describes a gel composition for inducing and stimulating hair growth and for reducing hair loss based on piperidinopyrimidine derivatives.
Oral in Conjunction with Topical Application
C. Catalfo, et. al., “Compositions Containing Minoxidil and Saw Palmetto for Treating Baldness”, U.S. Pat. No. 6,596,266 B2 (Jul. 22, 2003) describe compositions containing minoxidil as an active ingredient, other active agents and/or enhancer agents, such as saw palmetto extract and nettle root extract, and methods of using the compositions to treat male patterned baldness and to stimulate hair growth on the scalp.
Encapsulation
N. Weiner, et. al., “Stimulation of Hair Follicles”, U.S. Pat. No. 5,834,014 (Nov. 10, 1998) describe a novel method and delivery system for the topical delivery of a therapeutic weak acid or a base material, such as minoxidil, that utilizes a therapeutic material, which is modified to make it more hydrophilic, encapsulated in a lipid vesicle, preferably a non-phospholipid vesicle.
Problem
There remains in the art a need for an effective formulation and/or delivery method for delivery of minoxidil and/or a minoxidil salt.